title: The role of elevated autophagy on the synaptic plasticity impairment caused by CdSe/ZnS quantum dots.
abstract: It is well known that autophagy, a cellular stress response to degrade damaged components, can be activated by many nanoparticles. We have demonstrated that CdSe/ZnS quantum dots (QDs), which are widely applied in vitro for diagnostics and cellular imaging, can impair synaptic transmission and synaptic plasticity in the dentate gyrus (DG) area, but the mechanism is still unclear. Here we show that elevated autophagy is at least partly responsible for this synaptic dysfunction induced by QDs in vivo. QDs elicited autophagy in the HeLa cells and cultured hippocampal neurons as well, accompanied with GFP-light chain protein 3 (LC3) puncta dots and autophagosome formation, extensive conversion of LC3-I to LC3-II and a significant decrease of p62. Furthermore, we found that autophagy inhibitors (wortmannin, 3-MA or chloroquine) suppressed QDs-induced autophagic flux, partly blocked LTP impairment, coincident with down-regulation of synapsin-I and synapse deficits by QDs in the hippocampal CA1 area. Our studies have important implications in providing a potential clinical remedy for brain damage caused by nanomaterials and in designing safer nanoparticles.
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Miao
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Peipei
authors.initials: P
authors.lastname: Jin
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zha
authors.forename: Yuming
authors.initials: Y
authors.lastname: Chai
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Yunjiao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Jigui
authors.initials: J
authors.lastname: Zhang
authors.forename: Longping
authors.initials: L
authors.lastname: Wen
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D019187:Cadmium Compounds / Q000009:adverse effects* / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D045663:Quantum Dots / Q000009:adverse effects* / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000009:adverse effects* / Q000737:chemistry*; D009435:Synaptic Transmission / Q000187:drug effects; D017967:Zinc Compounds / Q000009:adverse effects* / Q000737:chemistry*
chemical_list: D019187:Cadmium Compounds; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D017967:Zinc Compounds; C118202:zinc selenite; C058667:cadmium selenide
keywords: 3-MA; 3-methyladenine; Autophagy; DG; DMEM; Dulbecco's modified Eagle's medium; FBS; HFS; I/O; IPI; LC3; LC3-I/II; LTP; PE; PPF; QD; QDs; ROS; Synapse density; Synapsin-I; Synaptic plasticity; TEM; dentate gyrus; fetal bovine serum; high frequency stimulation; input/output; inter-pulse interval; light chain protein 3; long-term potentiation; mTOR; mammalian target of rapamycin; paired-pulse facilitation; phosphatidylethanolamine; quantum dot; reactive oxygen species; transmission electron microscopy